Pyrrole dimethinecyanine dyes



Patented July 18, 1950 PYRROLE DIMETHINEOYANINE DYES v Robert H. Sprague and Leslie G. S. Brooker, Rochester, N. Y., assignors to Eastman Kodak Company, Rochester, N. Y., a corporation of New Jersey No Drawing. Application October 5, 1946,

Serial No. 701,396

4 Claims. (01. zso -zio) This invention relates to pyrrole dimethinecyanine dyes and to a'process for preparing them, ,This application is a continuation-inpart of our copending application, Serial No. 407,033, filed August 15, 1941 (nowUnited States Patent 2,409,612, dated 'oetober 22, 1946) which is a division of our application, Serial No. 317,726 filed February 7, 1940 (now U. S. Patent 2,298,731, dated Oetober lB, 1942,)

.In ourapplication 407,038, we have described pyrrole dimethinecyanine dyes which are useful as light-screening substances in photographic elements. These-pyrrole dimethinecyanine dyes while related in some respects to indole dimethinecyanine dyes"(purported to have been prepared by condensing an a-methylindole, diphenylformamidine and a cyclammonium quaternary salt containing a reactive methyl group, in the presence offace'tic anhydride), cannot be prepared in a manner analogous to that set forth for the indole dyes.

We have found certain new pyrrole dimethinecyanine dyes (some of which are disclosed in our parent application 407,033) and'these new dyes are of particular value intreatment of particular kinds of worm infestations. Our new compounds cannot be prepared in a manner analogous to that'set forth for the aforesaid indoledimethinecyanine dyes. It is, accordingly, an o bject of our invention to provide new compounds. A further object is to provide a process forpreparing these'new compounds. Other objects will become apparent hereinafter.

The new pyrroledimethinecyanine compounds of our invention can be represented by the following general formula:

ethyl, etc., X represents an anion, e. g. chloride,"

Hyl-CCH t R:- --R:

N i l. wherein R1 and R2 have the values given above,

with a quinoline quaternary salt selected from those which are represented by the following gen- 3 eral formula:

" wherein R, X and Z have the values given above. The condensations are advantageously effected" in the presence of a secondary amine, e; g. piperidine, 2-methylpiperidine, 3-methylpiperidine, 4- V methylpiperidine, 21,4 dimethylpiperidine, 2,6-

dimethylpiperidine, etc. The condensations are advantageously effected in a solvent, e. g. methyl,"

ethyl, n-propyl, isopropyl, n-butyl or isobutyl alcohols. p

The following examples will serve to illustrate further the manner of practicing our' invention.

Example ,1. II-methylquinoline (4) [2,5 di

methyl 1 phenylpyrrole (3) ldimethinecyanine iodide and chloride were filtered oifand washed with acetone-15.5 g.

(66 per cent yield) of orange brown crystals, of dye-iodide were obtained which after two recrystallizations from methyl alcohol had a melt Ila ing point of 263-265 C. with decomposition.

Analysis: I calc. 27.23; found 2682. The puri fled dye-iodide was converted to the dye-chloride by treating a boiling methylfalcoholic}solution of 11.8 g. of the dye-iodide withj the silver chloride prepared from 8.6 g. of silver nitrate." The solution was filtered from silver salts and concentrated to a small volume on a steam loath. The

dye-chloride was precipitated with diethyl ether and filtered off. It was dried. A yield.of .9.5..g.

of dye-chloride was obtained which is 47 percent yield. Brick red powder .melting at 261-262 C. with decomposition. 1

Analysis: Cl calm-9A6;found 9.l2. Example ,2.[2,5-dimethyle1-phenyZpyrrole- (.3) l' ,methinecydnine iodide and chloride 15.8 g. of B-methoxylepidine methiodide, 10 g. of 2,5-dimethyl-l-phenylpyrrole-3-carboxaldehyde, 300 cc. of methyl alcohol and 0.5 cc. of piperidine were .mixed .and refluxed ,forhours.

Th e dye ipdide -separated from the .hotsolution 0n stirring. The mixture was-chilled, :andithe dye-iodide collected on a filter.- It-waswashed with acetone. A yield of 15 g. (60 per cent),

orange needles was obtained which on recrystal g lization twice from methyl alcohol had a melting point of 259-261 C. with decomposition. Analysis: Lcalc. 25.58; found-25.63. 11.5- g. of purifieddye-iodidewas-converted to thedye-chloride .by treatment with silver .chloride prepared from 7.95;. of silver nitrate :in boilingmethyl alcohol. The silver salts were filtered off and the solution concentrated to a small volume rona steam .loath. The rdye-chloride was precipitated Withrdiethyl etherand filtered off. A yield .of..9.8 g. (46 per cent) of a brick red powder w'asobtained .of melting point 112.115 C. with decomposition. Analysis: -.(Jl calc. 8.7,6;-f o1 1nd 8.78.

43 in meth ylquinoline- 4.), 1, dimming cyanine iodide and chloride Example .3.gl1 n -am d-2.5-dimetl ylpyrrola.

27.72. 13.4 g. of dye-iodide was converted to dye-chloride by treatment with the silver chloride from 10 g. of silver nitrate in boiling methyl alcohol. The silver salts were filtered off and the solution was concentrated to a small volume. The dye-chloride was precipitated with .diethyl ether, andiwas filtered off and :dried. A ,yield of 10.1 g. of red powder was obtained which is a yield of 94 per cent.

Example 4.[1-n-amyl-2,5-dimethylpyrrole-(3) l '[71-ethylquinoline-(4)l dimethinecyanine iodide and chloride gl2 grflof lepidineiethiodide, 8 g. of 1-n-amyl-2,5- dimethylpyrrole-Becarboxaldehyde, 15 cc. of methyl alcohol.and0.5 cc. piperidine were mixed in a200 cc. flask and refluxed for 1 hours. The

solation was chilled in a refrigerator and the dyeiodide which separated was filtered ofi. It was washed .with acetone and then water and dried.

A yield of 9 g. (48 per cent) of small dark red needles was obtained which after two recrystallizations from ethyl alcohol had a melting point-df""1'85 C. with decomposition. Analysis: I cam. 26.7'lj found 26.49. 7.5 g. of 'the purified dye-iodide was converted "to the dye-chloride "by treatihg-a'boiling methyl alcohol solution with silver chloride from 5.4 g. of silver'nitrate. The silver salts were filtered ofiand the solution 'concentra'ted' to a small volume. The dye-chloride was precipitated with diethyl ether and filtered o'fin A yield of 439 g. of a red powder was obtained whichis a yield of 82 percent.

Eramplezfi; n .amyl 2;5-dimethylpyrrole RC-3):] L1-n-propylquinoline-(4ll dimethz'ne-' .cyam'ne iodide and chloride 11 2.5 g .of lepidine -n-.propiodide, -8 .g. .of l-namyhZ.5wdimethylpyrrole-3ecarboxaldehyde, 15. 0,0,;oimethylalcoholand 0.5 cc. piperidine .were; mixed in.a, flask andrefluxed .for 51 :hours. The solution was chilled in a refrigerator .and the dyeeiodide -.w.as .filtered off. .It was washed with aceteneand-then witlrwatenanddried. A yield 05.9.6 .g..'. (49 percent) -of darkred;needles was. obtained -which..had .a melting point of 466 167 C. with d ecompositiom'after two recrystallizations irom .ethylalcohol. Analysis: I calc. 26.00; found 26.10. 7.5g. of :purified dye-iodide was converted .to the dye-chloride by treatment -.of..a boiling.methyl alcoholicsolution of thedye-iodide with silver chloride .from:5.3 g. silver nitrate. The silver .salts were filtered ofi .and the .filtrate concentrated to a .small -volume 'on a (steam bath. Thedye-chloride is precipitated drom the residue with diethyl ether. It .was filtered-off and dried.

A yield of 5.8 g. of a redpowder was obtainedy which is a per cent recovery.

10.7 g. of lepidine-,3-hydroxyethobromide, 8 g. of..l-- .n am d-2,5-dimethylpyrrole-3-carboxa1- dehyde, 20-cc.-of.methyl alcohol-and.0.5 cc. .piper-,.

idinewere mixed in a .fiask-and refluxed for :1 hours- The dye-.iodideseparated in the hot. The reaction-mixture .was chilled ina refrigerator and then filtered off. The dye-iodide was washedwith acetone then with waterand dried. A yield of 10.4 g.(59 per cent) of .orange needles 'were obtained, which after two recrystallizations from ethyl alcohol had a melting point .of 200 -202 C,

with decomposition. Analysis: I calc. 18.03; found 18.28., 7.5 g. of purified dye-iodide was converted to dye-chloride by treatment of the boiling methyl alcoholicsolution with silver chloride from 5.4 g. silver nitrate. After four hours, the silver salts were filtered off and the filtrate concentrated to a small volume on a steam bath. The dye-chloride was precipitated from the cooled residue with diethyl ether. It was filtered and washed with diethyl ether. Ayield of 5 g.fof a reddish powder was obtained which is 83 per cent of the theoretical recovery.

Example 7.-[1-n-decyZ-2,5-dimethylpyrrole-(3) [1 -ethylquinolz'ne- (4) l-dimethinecyam'ne chloride 7.8 g. of lepidine ethiodide, 6.8 g. of l-n-decyl- 2,5-dimethylpyrrole-3-carboxaldehyde, cc. of methyl alcohol and. 0.3 cc. piperidine were mixed in a flask and refluxed for 1 hour. The solution was chilled in a refrigerator and then filtered 01f. The dye-iodide was washed lightly with acetone and then with water, and dried. A yield of 8.7 g. (61 per cent) of an orange powder was obtained which after two recrystallizations from ethyl alcohol had a melting point of 183-184 C. with decomposition. Analysis: I calc. 23.32; found 23.92. 7.4 g. of purified dye-iodide was converted to the dye-chloride by treatment of a boiling methyl alcoholic solution with the silver chloride from 4.6 g. silver nitrate. The silver salts were then filtered off and the filtrate concentrated to a small volume. From the residue the dye-chloride was precipitated with diethyl ether. It was filtered off and washed with diethyl ether and dried. A yield of 4 g. of an orange powder was obtained which is a recovery of 65 per cent. 7

In a manner similar to that disclosed in the above examples any of the pyrrolecarboxaldehydes of Formula II can be condensed with any of the quinoline quaternary salts of Formula III to give pyrroledimethinecyanine salts.

The dye-chlorides described above can be converted to dye-bromides by treating a hot methyl alcoholic solution of the dye-chloride with a concentrated aqueous solution of potassium bromide. The dye-bromide separates out, upon chilling, if necessary. The dye-iodides can be converted to the corresponding dyeperchlorates by treating a hot methyl alcoholic solution of the dye-iodide with a concentrated aqueous solution of sodium perchlorate. The dye-perchlorate separates out. Dye-thiocyanates can be made from dye-iodides by stirring the dyeiodide with a hot methyl alcoholic suspension of silver thiocyanate, filtering off the silver salts, and isolating the dye-thiocyanate from the methyl alcoholic solution. Dye-acetates can be prepared from dye-iodides in a similar manner using silver acetate instead of silver thiocyanate.

The herein-described dyes are of particular value in the treatment of worm infestations where the invading organism is of the class Nemotoda (round worms.) Among the various species of worms affected by these dyes are hookwor-ms, ascarids, filarids and whipworms.

The dyes containing an anion, such as chloride,

benzenesulfonate, p-toluenesulfonate, methylsulfate, ethylsulfate, acetate or propionate, are the more soluble dyes and the most useful therapeutically. In the above general Formula I, the compounds wherein the total number of carbon atoms contained in the two groups R and R1 is 6. from 5 to 18 are especially useful in the treatment of worm infestations. w 1

The pyrrolecarboxaldehydes employed herein can be prepared by condensing formamide with a pyrrole base selected from those represented by the following general formula? III. HC-CH Rt -Ra wherein R1 and Rz have' thevalues given above, in the presence of phosphorous oxychloride, according to the method of Nenitzeseu and Isacescu, Bull. Soc. Chim. Romania 11, (1929). Details of this preparation are also given by Brooker and Sprague Jour. Am. Chem. Soc. 67, 1869 (1945), and by Brooker and Sprague in their copending application Serial No. 407,033, filed August 15, 1941, The pyrrole bases of Formula III can be prepared according to the process of Lions et al., Proc. Royal Soc., New South Wales, 71, 92 (1937).

The quinoline quaternary salts employed herein can be prepared in known manner, by heating the quinoline bases with the appropriate alkyl salt, e. g. methyl iodide, methyl p-toluene-sulfonate, n-butyl bromide, dimethyl sulfate, etc. at temperatures of from about 90 to 0., heating the base and alkyl salt in a sealed tube where the alkyl salt is too volatile to permit suificient heating under reflux.

What we claim as our invention and desire to be secured by Letters Patent of the United States 1. The compounds which are represented by the following general formula:

/ C Hri l-O H:

wherein R. represents a primary alkyl group containing from 1 to 4 carbon atoms, R1 represents an aryl group of the benzene series, the total number of carbon atoms in the R and R1 groups being from 7 to 18, and X represents an anion.

2. The compound which is represented by the following formula:

OCH:

OHa

3. The compounds which are represented by the following general formula:

wherein X represents an anion.

2,515,905 7' 8 4. The compound which is represented. by the REFERENCES CI'JJED. followmg formula: The following references are of record in the OCH; file of this patent:

' 5 UNITED STATES PATENTS Number Name Date 2,051,134 Dieterle Aug. 18, 1936 ik L FOREIGN PATENTS 10 Number Country Date,

$0115 529,440 Great Britain Nov. 21-, 1940.

1 ROBERT H. SPRAGUE.

' LESLIE G. S. BROOKER. 

1. THE COMPOUNDS WHICH ARE REPRESENTED BY THE FOLLOWING GENERAL FORMULA: 